Biochemical characteristics of five retinal transmitter systems (acetylcholine, gamma-aminobutyric acid, dopamine, glutamate/aspartate and serotonin) have been established in the laboratory of the Principal Investigator. The overall goal of this proposal is to: 1) investigate the pharmacological sensitivity of these retinal transmitter systems, 2) determine the cellular/subcellular localization of both pre- and post-synaptic compartments of each transmitter system, 3) correlate two major physiologic activities, i.e., transretinal potentials and general metabolism, with neurotransmitter activities and 4) pursue current studies of synapto-synaptic interactions in retina by comparing pre- vs. post-synaptic receptor sites. Assessment of each transmitter system will be accomplished via assays of a variety of presynaptic activities (uptake, storage, synthesis, degradation and release) as well as postsynaptic activities (receptor binding, adenylate or guanylate cyclase stimulation, and lesioning by receptor-toxins). Pharmacological sensitivity will be determined in vitro as well as in vivo. Localization of transmitter systems will be accomplished using subcellular fractionation, autoradiographic and biochemical lesioning techniques. ERGs and general metabolic rates of isolated retina will be assessed using a continuous perfusion chamber with electrodes for ERG recordings and a radioassay for glycolytic activity. Synaptic interactions will be assessed by determining the stimulation or inhibition of presynaptic activities of one neurotransmitter system in synaptosomal fractions by the addition of a second neurotransmitter. This proposal will focus on four functional aspects of the neurotransmitters in retina and will produce integrated information about the role of chemical transmission in visual information processing in retina.